1429617-95-7Relevant academic research and scientific papers
Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2
Wang, Zhen,Zhang, Yali,Pinkas, Daniel M.,Fox, Alice E.,Luo, Jinfeng,Huang, Huocong,Cui, Shengyang,Xiang, Qiuping,Xu, Tingting,Xun, Qiuju,Zhu, Dongsheng,Tu, Zhengchao,Ren, Xiaomei,Brekken, Rolf A.,Bullock, Alex N.,Liang, Guang,Ding, Ke,Lu, Xiaoyun
, p. 7977 - 7990 (2018/09/06)
Discoidin-domain receptors 1 and 2 (DDR1 and DDR2) are new potential targets for anti-inflammatory-drug discovery. A series of heterocycloalkynylbenzimides were designed and optimized to coinhibit DDR1 and DDR2. One of the most promising compounds, 5n, ti
Discovery and optimization of 3-(2-(Pyrazolo[1,5- a ]pyrimidin-6-yl) ethynyl)benzamides as novel selective and orally bioavailable discoidin domain receptor 1 (DDR1) inhibitors
Gao, Mingshan,Duan, Lei,Luo, Jinfeng,Zhang, Lianwen,Lu, Xiaoyun,Zhang, Yan,Zhang, Zhang,Tu, Zhengchao,Xu, Yong,Ren, Xiaomei,Ding, Ke
supporting information, p. 3281 - 3295 (2013/06/04)
Discoidin domain receptor 1 (DDR1) is an emerging potential molecular target for new anticancer drug discovery. We have discovered a series of 3-(2-(pyrazolo[1,5-a]pyrimidin-6-yl) ethynyl)benzamides that are selective and orally bioavailable DDR1 inhibitors. The two most promising compounds (7rh and 7rj) inhibited the enzymatic activity of DDR1, with IC50 values of 6.8 and 7.0 nM, respectively, but were significantly less potent in suppressing the kinase activities of DDR2, Bcr-Abl, and c-Kit. Further study revealed that 7rh bound with DDR1 with a Kd value of 0.6 nM, while it was significantly less potent to the other 455 kinases tested. The S(35) and S(10) selectivity scores of 7rh were 0.035 and 0.008, respectively. The compounds also potently inhibited the proliferation of cancer cells expressing high levels of DDR1 and strongly suppressed cancer cell invasion, adhesion, and tumorigenicity. Preliminary pharmacokinetic studies suggested that they possessed good PK profiles, with oral bioavailabilities of 67.4% and 56.2%, respectively.
